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Publication : Endocardially Derived Macrophages Are Essential for Valvular Remodeling.

First Author  Shigeta A Year  2019
Journal  Dev Cell Volume  48
Issue  5 Pages  617-630.e3
PubMed ID  30799229 Mgi Jnum  J:272602
Mgi Id  MGI:6284164 Doi  10.1016/j.devcel.2019.01.021
Citation  Shigeta A, et al. (2019) Endocardially Derived Macrophages Are Essential for Valvular Remodeling. Dev Cell 48(5):617-630.e3
abstractText  During mammalian embryogenesis, de novo hematopoiesis occurs transiently in multiple anatomical sites including the yolk sac, dorsal aorta, and heart tube. A long-unanswered question is whether these local transient hematopoietic mechanisms are essential for embryonic growth. Here, we show that endocardial hematopoiesis is critical for cardiac valve remodeling as a source of tissue macrophages. Colony formation assay from explanted heart tubes and genetic lineage tracing with the endocardial specific Nfatc1-Cre mouse revealed that hemogenic endocardium is a de novo source of tissue macrophages in the endocardial cushion, the primordium of the cardiac valves. Surface marker characterization, gene expression profiling, and ex vivo phagocytosis assay revealed that the endocardially derived cardiac tissue macrophages play a phagocytic and antigen presenting role. Indeed, genetic ablation of endocardially derived macrophages caused severe valve malformation. Together, these data suggest that transient hemogenic activity in the endocardium is indispensable for the valvular tissue remodeling in the heart.
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